White Matter Connectivity and PD Cognitive Phenotypes

白质连接性和 PD 认知表型

• 批准号: 8632312
• 负责人: CATHERINE E PRICE
• 金额: $ 46.54万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-25 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8632312
• 关键词: Address; Affect; Age; Alzheimer' s Disease; Area; Behavior Therapy; Brain; Clinical; Clinical Research; Clinical Sciences; Cognition; Cognitive; Cognitive deficits; Country; Data; Data Set; Databases; Delayed Memory; Dementia; Development; Diagnosis; Diffusion; Disease; Episodic memory; Exhibits; Fiber; Functional Imaging; Gray unit of radiation dose; Heterogeneity; Hippocampus (Brain); Image; Imaging Techniques; Impaired cognition; Individual; Institutes; Intervention; Investigation; K-Series Research Career Programs; Matched Group; Measurement; Measures; Memory; Memory impairment; Methods; Modality; Movement Disorders; Neurodegenerative Disorders; Neuropsychological Tests; Neuropsychology; Parkinson Disease; Parkinson' s Dementia; Patients; Pattern; Phenotype; Population; Prefrontal Cortex; Psyche structure; Recruitment Activity; Relative (related person); Research; Resolution; Resources; Risk; Role; Sampling; Services; Severities; Short-Term Memory; Statistical Models; Surface; Symptoms; Translational Research; United States; Work; base; clinically relevant; cognitive change; cognitive function; disease phenotype; disorder control; entorhinal cortex; executive function; flexibility; gray matter; illness length; imaging modality; in vivo; information processing; meetings; memory process; neurocognitive test; neuroimaging; neuropsychological; neurorestoration; novel; peer; processing speed; public health relevance; standardize measure; therapy design; tool; white matter

Abstract Parkinson's Disease (PD) affects at least 1.5 million people in the United States alone. One of the most severe non-motor symptoms of PD is cognitive dysfunction involving reduced processing speed/working memory, and/or episodic memory. Relative to other neurodegenerative disorders with cognitive impairment, we know little about the neuroanatomical correlates of cognitive decline in PD. In preliminary work, we have examined brain connectivity associated with cognition in a group of idiopathic non-dementia PD relative to non- PD age-matched peers. Three distinct cognitive phenotypes were observed: a) slow information processing speed with preserved episodic memory, b) episodic memory difficulty with subtle slow information processing speed; and c) normal functioning with no deficits relative to age matched peers. Preliminary results of high angular resolution diffusion imaging suggest unique white matter and gray matter profiles: PD with episodic memory deficits exhibited mesial temporal circuit disruption (i.e., entorhinal-hippocampal connectivity); PD with primary processing speed deficits displayed aberration in the frontal-subcortical white matter circuitry (DLPFcircuit) between the dorsolateral prefrontal cortex and caudate; and PD without cognitive deficits showed circuitry similar to age-matched controls. The present study will recruit from one of the largest movement disorder databases in the country to investigate working hypotheses regarding memory and processing speed/executive difficulties and regional white matter connectivity within the temporal and frontal-subcortical regions, respectively. Three specific aims will be addressed. Aim 1: to demonstrate the association between memory function and the connectivity between the entorhinal cortex and hippocampus; Aim 2: to examine the relation between reduced processing speed/working memory and integrity within the DLPF cortex to caudate; and Aim 3: to reveal the significance of regional brain connectivity on memory or executive function decline at one and two years post-baseline. A research team specialized in movement disorders, functional and diffusion imaging, neuropsychological assessment, reliable change analyses, and longitudinal statistical modeling will carry out these aims. Study methods will draw from unique PD patient database, state-of-the art imaging techniques, and resources from the General Clinical Research Center within the Clinical and Translational Science Institute.

摘要 帕金森氏症(PD)仅在美国就至少影响了150万人。其中最 帕金森病严重的非运动性症状是认知功能障碍，包括处理速度/工作速度减慢 记忆和/或情节记忆。相对于其他有认知障碍的神经退行性疾病， 我们对帕金森病认知功能下降的神经解剖学相关性知之甚少。在前期工作中，我们有 研究了一组特发性非痴呆性帕金森病患者与非痴呆性帕金森病患者的大脑连接与认知功能的关系 PD年龄匹配的同龄人。观察到三种不同的认知表型：a)信息处理缓慢 保留情节记忆的速度，b)情节记忆困难，信息处理微妙缓慢 速度；c)功能正常，与年龄匹配的同龄人相比没有缺陷。HIGH的初步结果 角分辨率弥散成像提示独特的白质和灰质轮廓：伴有发作性帕金森病 记忆障碍表现为内侧颞叶回路中断(即，内嗅觉-海马区连接)； 初级加工速度缺陷表现为额叶-皮质下白质回路的异常 (DLPF环路)前额叶背外侧皮质与尾状核之间；无认知障碍的PD 与年龄匹配的对照组相似的电路。目前的研究将从最大的运动之一招募 该国的障碍数据库，以调查有关记忆和加工的工作假设 速度/执行困难与颞叶和额叶-皮质下的区域白质连接 区域。将解决三个具体目标。目标1：演示两者之间的关联 记忆功能和内嗅觉皮质和海马体之间的连接；目标2：检查 加工速度减慢/工作记忆减慢与DLPF皮质至尾状核的完整性之间的关系； 和目标3：揭示大脑区域连通性对记忆或执行功能下降的意义 基线后一年和两年。一个专门研究运动障碍的研究团队，功能性和 扩散成像、神经心理评估、可靠的变化分析和纵向统计 建模将实现这些目标。研究方法将来自独特的PD患者数据库，最先进的 影像技术，和来自临床和临床研究中心的资源 翻译科学研究所。